Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

203-T1 > Clinical aspects of the HPA > Flashcards

Clinical aspects of the HPA Flashcards

1
Q

Outline the HP axis

How is the system controlled?

A

BRAIN: Neurosecretory cells release bioaminergic or peptidergic hormone (median eminance, hypothalamus)

HYPOTHALAMUS: Releases releasing or inhibiting factors

Transported in blood via pituitary portal system

PITUITARY: Secretes trophic hormones (e.g. ACTH) which have an effect on a target organ

NEGATIVE FEEDBACK
Target-organ hormone secretion (e.g. cortisol) has an inhibitory effect on pituitary and hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the effect of the CRH neuron on the stress response?

A

Corticotropin releasing hormone (CRH) has both stimulatory and inhibitory effects on the stress response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which categories of hormone do the adrenal cortices secrete?

What enzyme is involved in the production of cortisol?

A
  1. Glucocorticoid (e.g. cortisol)
  2. Mineralocorticoid (e.g. Aldosterone)
  3. Sex hormones (e.g. androgens)

11-B-hydroxysteroid dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

State 6 effects of glucocorticoids?

A
  1. Maintenance of homeostasis in stress (e.g. haemorrhage, anxiety, infection)
  2. Anti-inflammatory
  3. Energy balance/metabolism
  4. Formation of bone and cartilage
  5. Regulation of BP
  6. Cognitive function, memory, conditioning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do patterns of release of glucocorticoids differ between mean data and individual data?

A

Mean data shows circadian rhythm

Individual data shows pulsatility of hormone release “Ultradian rhythm”- spontaneous pulses of varying amplitude

  • Amplitude lower than in circadian trough (in rats)
  • Hard to distinguish change in stress response (in humans)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens at a glucocorticoid receptor regarding the anti-inflammatory action of glucocorticoids?

A

Cortisol crosses cell membrane

Forms intracellular GR-HSP complex

Breakdown of complex, GR crosses nuclear membrane and sets off cascade of reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does the affinity of mineralocorticoid receptors change?

Effects of this?

A

In vitro, the mineralocorticoid receptor has the same affinity for aldosterone as cortisol

Specificity is conferred by a ‘pre-receptor’ mechanism

11-B-HSD2 in kidneys inactivated cortisol, enabling aldosterone to bind to the MR

  • '’Gating’’ of glucocorticoid access to nuclear receptors
  • amplification of GC signal in target cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give 5 symptoms of Cushing’s syndrome (too much cortisol)

A
  • Weight gain
  • Central obesity
  • Fractures
  • Neuropsychiatric disorders (Irritabiliy, depression)
  • Bruising
  • Oligo/amenorrhea
  • Erectile dysfunction
  • Muscle weakness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

State 5 clinical features of Cushing’s syndrome (too much cortisol)

A
  • (fat deposition over upper back, ‘buffalo hump’, rounded ‘moon’ face)
  • Thin arms and legs (central obesity)
  • Hirsutism
  • Thin skin, easily bruised, pigmented striae
  • Diabetes
  • Hypertension
  • Insulin resistance
  • Osteoporosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

State 4 causes of excess cortisol production (Cushing pathogenesis)

A
  • Pituitary adenoma: ACTH-secretory cells (a.k.a Cushing’s disease)
  • Adrenal tumor: adenoma (or carcinoma)
  • ‘Ectopic ACTH’: carcinoid, paraneoplastic
  • Iatrogenic: steroid treatment (‘Cushiingoid’)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

State 5 symptoms of Addison’s disease (too little cortisol)

A
  • Patient gradually deteriorates health
  • Languid and weak
  • Indisposed to either bodily or mental exertion
  • Body wastes
  • Slight pain is referred to stomach, occasionally vomiting
  • Discolouration of skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

State 3 clinical features of Addison’s disease (too little cortisol)

A
  • Hypoglycaemia
  • (Postural) hypotension
  • Malaise, weakness
  • Anorexia/ weight loss
  • Increased skin pigmentation: knuckles, palmar creases, mouth, scars
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

State 4 causes of primary adrenal insufficiency causing insufficient cortisol production

A
  • ‘Addison’s disease’
  • Autoimmune disease (common in UK)
  • Rarer causes: Metastases, TB
  • Decreased production of all adrenocortical hormones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

State 2 other causes of hypoadrenalism

A
  • Secondary to pituitary disease (rare)

- Iatrogenic- patients on high dose, long term steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Outline the difference between type 1 and type 2 autoimmune polyendocrine syndromes

A

TYPE 1

  • Rare
  • Onset in infancy
  • Ar (AIRE gene)
  • Common phenotype: Addison’s, Hypoparathyroidism, Candidiasis

TYPE 2

  • Commoner (still rare)
  • Onset: Infancy to adulthood
  • Polygenic
  • Common phenotype: Addison’s, T1DM, AI Thyroid disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is common about autoimmune diseases?
What are the clinical implications of this?

Give 3 examples of autoimmune disease

A

They may occur together
- High index of suspicion for addition AI endocrine disorders. Consider screening these patients
e.g. T1DM + fatigue, weight loss + hypos –> Addisons?
T1DM + non-specific GI symptoms + diarrhoea –> Coeliac

e.g. T1DM, AITD, gestational/postpartum thyroiditis, coeliac disease, Addison’s, Pernicous anaemia, Alopecia, Vitiligo, Heptatitis, Premature ovarian failure, myaesthenia gravis

17
Q

How do we assess the HPA?

A

BASAL

  • Blood: cortisol, ACTH
  • Urine: Cortisol (requires 24 hour collection)
  • Saliva: Cortisol (timing is important, no stress)
    • Be aware of circadian/ ultradian rhythm

DYNAMIC

  • Stimulated test? (ACTH, CRH, ‘stress’ —> hypoglycaemia)
  • Suppressed function? –> Dexamethasone (synthetic glucocorticoid
18
Q

CLINICAL APPLICATION

Typical results for too much cortisol?

A
  1. Area under 24 hour urine collection curve indicative (LARGER)
  2. Midnight cortisol (blood, saliva) - ‘trough’
  3. 9am ACTH (with paired cortisol)
    - Pituitary/ adrenal/ ectopic ? —> Dexamethasone suppression
    • sensitive to GC negative feedback @pituitary
19
Q

What is the dexamethasone test?

A
  • used to assess adrenal gland function by measuring how cortisol levels change in response to an injection of dexamethasone
  • It is typically used to diagnose Cushing’s syndrome.
  • Dexamethasone is an exogenous steroid that provides negative feedback to the pituitary gland to suppress the secretion of (ACTH).
  • It binds to glucocorticoid receptors in the anterior pituitary gland, which lie outside the blood-brain barrier, resulting in regulatory modulation.
  • A high dose of dexamethasone exerts negative feedback on pituitary neoplastic ACTH-producing cells (Cushing’s disease), but not on ectopic ACTH-producing cells or adrenal adenoma (Cushing’s syndrome)
20
Q

CLINICAL APPLICATION

Typical results for too little cortisol?

A
  1. 9am cortisol - ‘PEAK’
  2. SYNACTHen test: adrenal response to ACTH
    - trophic effect ACTH on adrenals
  3. Insulin tolerance test
    - response to hypoglycaemic stress (can be dangerous!)
  4. U&E (Low Na, High K) in Addison’s
    - due to mineralocorticoid deficiency
    - can measure RENIN & ALDOSTERONE concentration
  5. Low glucose
21
Q

CLINICAL APPLICATION

Comment on when you should investigate/ image for endocrine disorders

A
  • Never investigate for endocrine condition unless symptoms and signs indicate. –> Risk of false positive result
  • Never image and endocrine gland until you have established the diagnosis biochemically –> Risk of discovering incidentalomas
  • Once confirmation of Cushing’s: CXR/MRI pituitary/CT adrenals
  • Addison’s patients rarely need imaging unless concern for TB/metastatic cancer
22
Q

CLINICAL APPLICATION

How is Cushing’s managed?

A
  1. Surgical intervention
    - transphenoidal adenectomy
    - adrenalectomy
  2. Pituitary radiotherapy
23
Q

CLINICAL APPLICATION

How is Addision’s managed?

A
  1. Steroid hormone replacement therapy
    - glucocorticoid (usually hydrocortisone over prednesolone)
    - dose needs to be increases to cover ‘stressors’ e.g. intercurret illnesses (flu), operations/post-op period
    - IV/IM if unable to take pill due to: Nil-mouth, vomiting
  2. Primary adrenal insufficiency need mineralocorticoid replacement therapy (fludrocortisone)
  3. Secondary adrenal insufficiency dont need fludrocortisone (take other hormone replacement)
24
Q

CLINICAL APPLICATION

What should be noted about patients on steroids?

A
  1. May be on long term, high dose use (e.g. on glucocorticoids) which may suppress endogenous adrenal function
    - May be used for anti-inflammatory and anti-immune properties in severe asthma/COPD, temporal artheritis/ polymyalgia rheumatica
  • May appear ‘Cushingoid’
  • May not mount adequate ‘stress response’
  • Steroid treatment SHOULDN’T be stopped suddenly
  • Give loading dose for operations
  • They should be given ‘steroid treatment card’ to remind doctors

203-T1 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions